Endometrial cancer is the most common gynecologic malignancy of the female genital tract. Estrogen exposure is the major clinical risk factor for the development of endometrial cancer. On the molecular level, expression of the tumor suppressor PTEN is lost in 50-80% of early endometrial lesions. However, how PTEN loss promotes estrogen-driven endometrial carcinogenesis has not been characterized. Our long-term objective is to characterize the molecular mechanisms involved in endometrial carcinogenesis. Recent evidence suggest that Epidermal Growth Factor (EOF) signaling can crosstalk with the Estrogen Receptor (ER), leading to increased signaling through ER. To assess this as a possible factor in endometrial cancer we will use cultured endometrial epithelial cells to study how PTEN and EGF pathways affect ER responsive genes at the molecular level. Our specific aims are to 1) characterize the role of PTEN on estrogen receptor signaling in endometrial cancer cells 2) determine the effect of EGF on ER transcriptional activity in endometrial cancer cells 3) and to determine the role of the p160 family of coactivators in EGF/ER crosstalk. [unreadable] [unreadable]